Significance: Approximately 1.4 million victims of Traumatic Brain Injury (TBI) are seen in emergency departments each year in the U.S. and, of those, 50,000 die and 235,000 are hospitalized. A least 2% of the U.S. population has a TBI-related long-term need for help to perform activities of daily living. There is growing evidence that the management of TBI in the early minutes after injury profoundly impacts outcome. This has led to the promulgation of evidence-based TBI treatment guidelines by authoritative national and international scientific bodies. Reports on guideline implementation in the hospital setting are very promising. However, no studies have evaluated their impact in the prehospital setting. While randomized prehospital trials to identify the effectiveness of the guidelines would clearly be optimal, the strong indirect evidence currently precludes withholding guideline therapy because of ethical considerations. Thus a large, prospective, historically controlled, observational study is the best methodology currently available to evaluate the effectiveness of implementing the guidelines in the prehospital setting. Specific Aim: To test the hypothesis that implementation of the TBI guidelines in a statewide EMS system will reduce mortality and improve non-mortality outcomes in adults and older children (age e18) with severe TBI. Objective #1: Implement the nationally-vetted TBI guidelines across a broad variety of EMS systems (urban, suburban and rural) throughout the State of Arizona. This will be accomplished through the statewide collaboration between the University of Arizona, the Arizona Department of Health Services, and local EMS agencies responding to 85% of the state's population. This will mirror the approach that has been successfully employed to study and document a tripling of patient survival from out-of-hospital cardiac arrest in the state. Objective #2: Collect prehospital EMS and trauma center data on severe TBI patients cared for by participating EMS agencies to determine pre-implementation and post-implementation injury severity/risk- adjustment measures and outcomes. Objective #3: Evaluate the impact of prehospital guideline implementation on the following outcomes: 1) Overall mortality (primary outcome), 2) mortality among patients who are intubated prior to hospital arrival, 3) non- mortality outcomes such as hospital/intensive care unit length of stay, ventilator days, and patient disposition, and 4) 6-month functional/neurological status. Relevance/health impact: The societal burden of TBI is immense. While the potential for dramatically reducing morbidity and mortality by early treatment appears to be great, the effectiveness of the prehospital guidelines remains unproven. Demonstrating the impact of guideline therapy would potentially lead to widespread implementation of the effective interventions. This could dramatically reduce morbidity and mortality from this major public health problem. On the other hand, if the guidelines are not effective despite confirmed implementation across a wide variety of EMS systems throughout the entire state, this would provide the ethical basis for conducting future randomized trials. PUBLIC HEALTH RELEVANCE: The impact of Traumatic Brain Injury (TBI) on society is enormous: approximately 1.4 million victims of TBI are seen in emergency departments each year in the U.S. and, of those, 50,000 die and 235,000 are hospitalized. Authoritative scientific bodies have promulgated evidence-based TBI treatment guidelines and the potential for dramatically reducing morbidity and mortality from TBI by implementing these nationally-vetted guidelines in the prehospital setting appears to be great. However, the effectiveness of these guidelines remains unproven for care delivered outside of the hospital. Validating the impact of these treatment guidelines in Emergency Medical Services systems would potentially lead to widespread implementation and, thereby, reduce morbidity and mortality from this immense public health problem.